PROJECT SUMMARY/ABSTRACT The goal of the T32 Investigational Cancer Therapeutics Training Program (ICTTP) at Memorial Sloan- Kettering Cancer Center (MSKCC) is to provide highly select physician trainees in hematology and medical oncology with the research training necessary for successful careers in the translation of cancer biology discoveries into novel molecular, immune, or cell-based therapeutics, and those experimental treatments into clinical trials that have the potential to change standards of care. The T32 ICTTP program accomplishes this goal by combining a comprehensive mentored training program, an extensive didactic curriculum in clinical and translational research methodologies, and experiential programs supporting development of the critical career skills (e.g. collaboration, research management, grant writing) necessary for academic success. Each year, we select 4 highly committed postdoctoral trainees from the pool of outstanding physicians at MSKCC who have completed at least 3-4 years of both internal medicine and oncology/hematology clinical training. T32 trainees are then supported for 2 consecutive years so that ? 80% of their time and effort is dedicated to research training. Based on individual research interests and career goals, ICCTP trainees develop either a laboratory- based or a prospective clinical research program with guidance from their mentors, who are established, independently funded investigators. These programs involve extensive collaborative scientific interactions, including additional clinical scientist mentorship for laboratory-based trainees and laboratory scientist mentorship for clinical research trainees. The T32 ICTTP supplements mentored research training with a curriculum of symposia, workshops, in-person didactic programs, and online courses that prepares trainees to conduct successful, independently supported research at the faculty level. We continue to enhance the program by revising and adding new educational programs in clinical research methodology, research ethics, national and international clinical trial requirements and conduct, as well as hands-on writing workshops for grants and protocols. Participating faculty mentors are continually reviewed and selected based on strict criteria for research productivity, independent funding, and quality of mentoring. T32 ICTTP mentors have research programs on cancer genetics, genomics, epigenetics, signal transduction, and metabolism; tumor immunology and immunotherapy; drug and cellular therapeutic development; and tumor evolution, using systems and computational approaches. Projects conducted by T32 ICTTP trainees in the proposed funding period continue similar themes in cancer therapeutics research. All T32 ICTTP graduates from the last funding cycle are continuing in oncology research, and all who are working in academia have secured independent research funding. This success continues the ICTTP?s 40-year track record of training leaders in cancer therapeutic development and translational research.